Journal of Oral Pathology & Medicine最新文献

Background: Cystadenoma of the salivary glands (CSG) is a rare benign, multicystic neoplasm, representing approximately 1%-4.7% of all benign salivary gland tumors. This study aimed to systematically review the clinicopathological data reported on case reports and case series of CSG.

Methods: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Comprehensive searches were performed across PubMed, Web of Science, Scopus, and Embase electronic databases.

Results: A total of 81 studies were included, encompassing 126 cases of CSG. A slight female predominance was observed (54.91%), with a mean patient age of 54.2 ± 21.5 years. The median lesion size was 1.4 ± 1.6 cm. The parotid gland was the most affected site (23.47%). Most cases were asymptomatic (86.58%), and nodular presentation was noted in 70.96%. Mucocele was the most suspected clinical diagnosis. Histopathologically, the papillary subtype was predominant (67.03%), with oncocytic cells prevailing, followed by columnar and cuboidal cell types. Of the 57 cases with available data on growth pattern, 38 were multicystic and 19 unicystic. Immunohistochemical analysis frequently involved the use of p63, MUC4, MUC1, and CK7. All cases were managed surgically, with a recurrence rate of 6.25%. The median follow-up period was 12.1 ± 23.2 months.

Conclusion: CSG is a rare benign tumor that predominantly affects the parotid gland in female patients, typically presenting as a multicystic lesion. Surgical excision remains the treatment of choice, with a generally favorable prognosis.

Background: Autophagy and tumor necrosis factor-alpha (TNF-α) are pivotal in the progression of oral squamous cell carcinoma (OSCC), yet their interplay remains inadequately understood. This study aims to evaluate the interaction between autophagy and TNF-α for OSCC progression.

Methods: Cytokine levels were measured with the Bio-plex assay; autophagy activation was visualized by confocal microscopy. NF-κB p65 activity was assessed via reporter assay, and cell growth was evaluated using CellTiter-Glo, clonogenic assay, and flow cytometry. Clinical data were analyzed using SPSS.

Results: The level of TNF-α decreased in OSCC cells treated with an autophagy inhibitor but increased in OSCC cells under starvation as an autophagy-inducing condition. The production of TNF-α was also lower in OSCC cells knocked down with siULK1 plus siBECN1 or siATG5 plus siATG7 when compared with OSCC cells knocked down with scrambled siRNA under starvation conditions. The addition of TNF-α increased levels of autophagosome and autolysosome in OSCC cells-TNF-α induced expressions of LC3 and P62 by activating RelA. OSCC cells exposed to TNF-α exhibited increased cell viability and autophagy inhibitors reversed the increased cell viability and growth. TNF-α levels were higher in the serum of OSCC patients than in those with precancerous conditions. Elevated levels of TNF-α were linked to poorer disease-specific survival in OSCC patients. The expression of RelA showed a positive correlation with the expression of LC3 and PP62 in OSCC patients. The increased co-expression of TNF-α/P62, TNF-α/LC3, and TNF-α/RelA/PP62 was associated with shorter disease-free survival in OSCC patients.

Conclusion: The reciprocal regulation between TNF-α and autophagy may contribute to tumor progression in OSCC.

Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck, and its therapeutic efficacy critically depends on the identification of reliable biomarkers. This study investigates the interplay between m6A methylation-related biomarkers and OSCC progression biomarkers, aiming to enhance the understanding of pathogenic mechanisms and facilitate personalized treatment strategies.

Methods: Based on multi-dimensional bioinformatics analyses-including differential expression, enrichment, prognostic modeling, and immune infiltration analyses-of GEO and TCGA datasets, potential biomarkers that promote malignant progression in OSCC and their association with m6A-related molecules were identified. The effect of MAD2L1 on OSCC in vitro was assessed using CCK-8, RT-qPCR, colony formation, wound healing, and TUNEL assays, while Western blotting was employed to explore the underlying mechanisms by which MAD2L1 influences OSCC progression. Additionally, RT-qPCR was used to examine the impact of MAD2L1 on m6A-related biomarkers. Finally, a xenograft tumor model was utilized to evaluate the effect of MAD2L1 on tumor growth in vivo.

Results: Our findings demonstrate that MAD2L1 serves as a biomarker associated with the progression of oral squamous cell carcinoma (OSCC). Specifically, MAD2L1 expression was significantly upregulated in OSCC patients and positively correlated with increasing histopathological grade. Elevated MAD2L1 expression was linked to poor prognosis in OSCC patients and enabled the construction of an effective prognostic model. Furthermore, MAD2L1 expression showed significant positive correlations with multiple m6A-related biomarkers. Knockdown of MAD2L1 reduced the mRNA expression of THDC1, WTAP, and RBMX. In addition, MAD2L1 expression was significantly associated with tumor microenvironment (TME) dysregulation. Finally, both in vitro and in vivo experiments confirmed that MAD2L1 knockdown markedly suppressed OSCC cell growth.

Conclusion: Collectively, our study identifies MAD2L1 as a promising oncogenic biomarker and therapeutic target in OSCC, whose upregulation drives tumor progression, impairs patient prognosis, and disrupts m6A modification.

Background: The packaging and marketing of electronic cigarettes (e-cigs) often target younger demographics. This study aimed to evaluate gene expression in e-cig users through exfoliative cytology.

Methods: Samples were collected from 17 e-cig users and 10 nonsmokers as controls. Clinical data included age, gender, heart rate, oximetry, capillary blood glucose, carbon monoxide levels, sialometry, alcohol-related risk scores, alcohol consumption, and e-cig use parameters. Smears from the left tongue edge were obtained using a Rovers Orcellex Brush. The Papanicolaou method assessed epithelial maturation and cytological features, categorized from normal to conclusive for malignancy. Cellular composition, inflammation, microbial presence, and atypia were evaluated using a semiquantitative scoring system. Gene expression (p16, IL1-beta, CXCL8, TNF, and KRT13) was analyzed by RT-PCR. Statistical comparisons used the Mann-Whitney test, and correlations were assessed via Spearman's test (p ≤ 0.05).

Results: Fruit flavors were the most preferred. Some users were former smokers (average abstention: 3.15 months). Bacterial colonies were more prevalent in the e-cig group (64.7% vs. 20%, p = 0.085), mucus and inflammatory changes were found exclusively in e-cig users (p = 0.062). No significant differences were found in the Papanicolaou classification by gender (p = 0.904). Gene expression analysis showed a differential expression of p16 and TNF between the groups. Significant correlations were found between carbon monoxide and p16 expression (r = -0.41, p = 0.02), vaping sessions per day and p16 expression (r = -0.37, p = 0.02), and daily alcohol dose and TNF expression (r = -0.42, p = 0.04).

Conclusion: E-cigarette use may induce early molecular and cytological changes in the oral mucosa, affecting inflammation, immunity, and epithelial differentiation.

Background: Oral submucous fibrosis is a progressive, oral potentially malignant condition that can affect the oral cavity and is often linked to areca nut consumption. This study aimed to investigate the potential of dental pulp mesenchymal stem cells secretome (DPMSCs-S) in the reversal of areca nut-induced fibrosis in human fibroblast cells and patient-derived buccal mucosa tissues.

Materials and methods: The cytokine and growth factor levels in DPMSCs-S were analyzed by flow cytometry. Cytotoxicity and apoptotic features were analyzed using a cell viability assay and microscopy, respectively. Cellular senescence and reactive oxygen species generation were assessed in human fibroblast cells using a β-galactosidase assay and 2',7'-dichlorodihydrofluorescein diacetate probe, respectively. Fibrosis-related gene expression (COL15A1, COL1, COL3, α-SMA, TGFβ1, and TGFβ2) and protein expression (COL1 and Ki67) were assessed by RT-PCR and fluorescence microscopy, respectively.

Results: Areca nut extract and arecoline resulted in a dose-dependent reduction in cell viability. Secretome treatment reduced cell death, apoptotic and senescent features in fibroblast cells exposed to areca nut extract and arecoline, decreased ROS levels, and significantly downregulated areca nut-induced fibrotic gene expressions (COL15A1, COL3, α-SMA, TGFβ2), and protein expression of COL1. Heat-inactivated secretome retained the activity, implying the involvement of heat-stable biomolecules in the reversal of fibrosis. Ex vivo results corroborated these findings, with reduced expression of COL15A1, COL3, and α-SMA in buccal tissues from oral submucous fibrosis patients treated with DPMSCs-S.

Conclusion: Secretome exhibited promising cytoprotective and anti-fibrotic properties, reduction in cell death, senescence, collagen expression, and oxidative stress. These findings support the potential of secretome as a novel therapeutic candidate for oral submucous fibrosis, meriting further investigation in preclinical and clinical trials.

Background: Hereditary gingival fibromatosis (HGF) is a rare, genetically heterogeneous disorder characterized by benign, slowly progressive fibrous overgrowth of the gingiva. This study aimed to identify the pathogenic genes responsible for non-syndromic HGF and to elucidate the activation mechanism for truncated SOS1 protein.

Methods: Genomic DNA was extracted from peripheral blood samples of two unrelated Han Chinese families with non-syndromic HGF. Whole-genome sequencing (WGS) was utilized to identify pathogenic mutations. Bioinformatic analyses were conducted to predict the deleteriousness of the identified mutations. The phenotypic spectrum of SOS1 mutations was summarized by literature review methods, with a particular focus on the gingival hyperplasia phenotype. Genotype-phenotype correlations were analyzed.

Results: WGS identified two novel SOS1 mutations, c.3262dupA/p.Thr1088fs and c.1523A>G/p.Asn508Ser in two unrelated Han Chinese families with non-syndromic HGF. MutationTaster and CADD revealed the c.1523A>G/p.Asn508Ser mutation as disease-causing. The mutational spectrum of SOS1 showed a predominance of missense mutations, among which three were linked to the gingival hyperplasia phenotype. Frameshift mutations in the C-terminal region of SOS1 were all associated with the gingival hyperplasia phenotype. A novel "Dual-Gated Model" was introduced to elucidate the activation mechanisms for both the normal and truncated forms of SOS1.

Conclusions: Our study identified two novel SOS1 mutations, c.3262dupA/p.Thr1088fs and c.1523A>G/p.Asn508Ser, in two unrelated Han Chinese families with non-syndromic HGF. A novel "Dual-Gated Model" was proposed to elucidate the full activation process of wild-type and truncated SOS1. We extended the mutational spectrum of SOS1 in non-syndromic HGF and provided new insights on the molecular mechanism of pathogenesis.

Introduction: Dysregulated expression of urokinase-type plasminogen activator (PLAU), a serine protease, is frequently associated with various cancers. However, in oral squamous cell carcinoma (OSCC), the specific biological functions and mechanisms of action of PLAU remain unclear.

Methods: Western blot (WB) analysis and quantitative real time polymerase chain reaction experiments verified the protein and mRNA expression of PLAU in oral squamous cell carcinoma; Flow cytometry was used to assess changes in OSCC cell cycle and apoptosis following PLAU knockdown. Transwell assays were conducted to evaluate alterations in cell invasion and migration after PLAU knockdown. LinkedOmics database was employed to analyze the correlation between PLAU and TGF-β1.

Results: Our study using GEPIA2 dataset analysis and WB experiments revealed that PLAU expression was upregulated in HNSC tissues and OSCC cell lines and was significantly associated with overall survival in patients. Furthermore, the invasive and migratory abilities of UM1 cells were significantly reduced following PLAU knockdown, as demonstrated by scratch assays and Transwell migration assays. Subsequently, Western blot analysis revealed that PLAU knockdown effectively inhibited the epithelial-mesenchymal transition (EMT) process. Meanwhile, LinkedOmics database analysis revealed a significant positive correlation between TGF-β1 and PLAU. Further investigations demonstrated that TGF-β1 induces PLAU upregulation, which subsequently promotes the migration, invasion, and EMT process in OSCC cells. Conversely, PLAU knockdown abrogates these TGF-β1-mediated effects.

Conclusion: PLAU acts as a key oncogenic driver in OSCC and may serve as a potential diagnostic and prognostic biomarker. More importantly, the TGF-β1-PLAU axis may offer new therapeutic targets for OSCC treatment.

Introduction: Chronic hyperplastic candidiasis (CHC) has a controversial potential role in the carcinogenesis of oral epithelium. In addition, histological overlap between CHC and atypical epithelial proliferation with Candida (AEPC) may cause a diagnostic dilemma. In this pilot study, potential premalignant markers including tumor suppressor gene proteins p53 and p16, and cancer stem cell markers CD44 and OCT4, were investigated in CHC and AEPC with benign and malignant validation groups.

Materials and methods: A total of 20 tongue lesions were identified, with 5 cases of each: benign validation group of traumatic fibroma, CHC without dysplasia, AEPC, and malignant validation group of moderately differentiated squamous cell carcinoma (SCCA). IHC staining was performed with p53, p16, CD44, and OCT4. Inter-observer variability between two pathologists' independent scores was determined using Cohen's kappa (k). A third pathologist served as tiebreaker for disagreement. Chi-square testing was performed between diagnostic groups and staining results.

Results: Overall agreement of staining for all stains was good (κ = 0.614) for intensity, moderate (κ = 0.544) for percentage, and good (κ = 0.612) for p53 wild or atypical pattern analysis (based on prior studies). p53 and CD44 staining showed statistically significant differences between the fibroma/CHC cases and the AEPC/SCCA cases. The most diagnostic measures were p53 pattern, which categorized 100% of fibroma/CHC cases as wild type and 90% of AEPC/SCCA groups as atypical (p < 0.001), and CD44 staining above 50%, which diagnosed 70% of AEPC/SCCA cases versus 0% of fibroma/CHC cases (p = 0.004). Using these two together, all AEPC/SCCA cases were diagnosed. p16 and OCT4 were not significant in differentiating between diagnoses in this study.

Conclusions: In this pilot study, p53 pattern and CD44 percentage showed significant potential to serve as useful diagnostic aids. Future studies with larger sample sizes are necessary to validate these findings and explore the potential of these markers in determining the transformation risk of CHC and AEPC.

Background: Human papillomavirus (HPV)-16 is the most commonly found HPV-type in HPV-induced oropharyngeal squamous cell carcinomas (OPSCC). The serological response to HPV oncoproteins could be a way to detect HPV-driven OPSCC early. A rapid test for the detection of HPV16 L1 antibodies in blood was developed in 2015 (PrevoCheck).

Methods: Prospectively, we included 42 patients with newly diagnosed head and neck squamous cell carcinomas (HNSCC). Pretreatment venous blood samples were collected and analyzed with PrevoCheck. The results were interpreted by 2 reviewers. Immunohistochemistry with p16 and HPV DNA-PCR testing served as a reference standard.

Results: Sixteen patients had HPV-positive tumors (38.1%). PrevoCheck showed 2 true positives, 26 true negatives, 0 false positives, and 14 false negatives, which resulted in a sensitivity of 12.5% (95% CI: 1.6%-38.4%) at a specificity of 100% (95% CI: 86.8-100). Interobserver agreement showed perfect agreement.

Conclusion: A negative result in a test with a high sensitivity can be used to rule out disease, that is, HPV16-related HNSCC. We found 14 false negative results, resulting in low sensitivity for PrevoCheck. This test does not seem suitable to screen for HPV16-related head and neck cancers.